Uncomplicated Malaria Infection Research Articles

Efficacy and safety of artemether-lumefantrine against uncomplicated falciparum malaria infection in Tanzania, 2022, a single arm clinical trial.

Artemether-lumefantrine (AL) is the first line anti-malarial drug for the treatment of uncomplicated malaria in Tanzania. The World Health Organization (WHO) recommends regular efficacy monitoring of anti-malarial drugs to inform case management policy decisions. This study assessed the safety and efficacy of AL for treating uncomplicated P. falciparum malaria in Tanzania in 2022. Children 6 months to 10 years with uncomplicated P. falciparum malaria were recruited from four sentinel sites and treated with the standard 6 dose, 3-day regimen for AL. Clinical and parasitological responses were monitored for 28 days using the WHO standard protocol. Genotyping based on msp1, msp2 and glurp was used to distinguish recrudescence from reinfection. SANGER sequencing was used to detect K13 mutations. 352 participants, 88 per site, were enrolled. Four withdrew and 55 experienced parasite recurrence. The PCR corrected Kaplan-Meier efficacies were, 89.9% in Pwani, 95.0% in Kigoma, 94.4% in Tanga, and 98.9% in Morogoro. No K13 mutations were found. Artemether-lumefantrine remains highly efficacious in three regions of Tanzania but the PCR-corrected efficacy in Pwani fell below the WHO-defined 90% threshold at which policy change is recommended. Implementing strategies to diversify ACTs to ensure effective case management in Tanzania is critical.

Relationship between calcium-to-magnesium ratio and malaria parasite density among children with uncomplicated malaria infection

Relationship between calcium-to-magnesium ratio and malaria parasite density among children with uncomplicated malaria infection

Efficacy of artesunate-amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria in mainland Tanzania

BackgroundDiversification of artemisinin-based combination therapy (ACT) is suggested as one of the strategies that can be used to contain artemisinin resistance. Artesunate-amodiaquine (ASAQ) is one of the artemisinin-based combinations that can be used in the diversification strategy as an alternative first-line treatment for uncomplicated malaria in mainland Tanzania. There is however limited data on the efficacy of ASAQ in mainland Tanzania. This study assessed the efficacy of ASAQ for treatment of uncomplicated Plasmodium falciparum malaria in selected sentinel sites for therapeutic efficacy studies in mainland Tanzania.MethodsBetween December 2018 and March 2020, children aged between 6 months and 10 years, attending at Nagaga, Mkuzi, and Mlimba primary health facilities, and with suspected uncomplicated malaria infection were screened for eligibility to participate in the study. Malaria infection was screened using microscopy. Children with uncomplicated P. falciparum monoinfection and who fulfilled all other inclusion criteria, and had none of the exclusion criteria, according to the World Health Organization (WHO) guidelines, were treated with ASAQ. Follow-up visits were scheduled on days 0, 1, 2, 3, 7, 14, 21, and 28 or on any day of recurrent infection for clinical and laboratory assessment. Polymerase chain reaction (PCR)-corrected cure rate on day 28 was the primary outcome.ResultsA total of 264 children, 88 in each of the three study sites (Mlimba, Mkuzi and Nagaga health facilities) were enrolled and treated with ASAQ. The ASAQ PCR-corrected cure rate was 100% at all the three study sites. None of the participants had early treatment failure or late clinical failure. Furthermore, none of the participants had a serious adverse event.ConclusionASAQ was highly efficacious for the treatment of uncomplicated P. falciparum malaria in mainland Tanzania, therefore, it can be deployed as an alternative first-line treatment for uncomplicated malaria as part of diversification strategy to contain the spread of partial artemisinin resistance in the country.

Host-parasite interaction in severe and uncomplicated malaria infection in ghanaian children.

During malarial infection, both parasites and host red blood cells (RBCs) come under severe oxidative stress due to the production of free radicals. The host system responds in protecting the RBCs against the oxidative damage caused by these free radicals by producing antioxidants. In this study, we investigated the antioxidant enzyme; superoxide dismutase (SOD) activity and cytokine interactions with parasitaemia in Ghanaian children with severe and uncomplicated malaria. One hundred and fifty participants aged 0-12 years were administered with structured questionnaires. Active case finding approach was used in participating hospitals to identify and interview cases before treatment was applied. Blood samples were taken from each participant and used to quantify malaria parasitaemia, measure haematological parameters and SOD activity. Cytokine levels were measured by commercial ELISA kits. DNA comet assay was used to evaluate the extent of parasite DNA damage due to oxidative stress. Seventy - Nine (79) and Twenty- Six (26) participants who were positive with malaria parasites were categorized as severe (56.75 × 103 ± 57.69 parasites/µl) and uncomplicated malaria (5.87 × 103 ± 2.87 parasites/µl) respectively, showing significant difference in parasitaemia (p < 0.0001). Significant negative correlation was found between parasitaemia and SOD activity levels among severe malaria study participants (p = 0.0428). Difference in cytokine levels (IL-10) amongst the control, uncomplicated and severe malaria groups was significant (p < 0.0001). The IFN-γ/IL-10 /TNF-α/IL-10 ratio differed significantly between the malaria infected and non- malaria infected study participants. DNA comet assay revealed damage to Plasmodium parasite DNA. Critical roles played by SOD activity and cytokines as anti-parasitic defense during P. falciparum malaria infection in children were established.

Dihydroartemisinin-piperaquine treatment failure of uncomplicated Plasmodium falciparum malaria infection in a traveller.

We report a late dihydroartemisinin–piperaquine treatment failure of uncomplicated Plasmodium falciparum malaria infection in a traveller without evidence of drug resistance. The correct treatment intake was confirmed, isolates drugs susceptibility was confirmed by RSA-PSA and chemosusceptibility. No molecular markers associated with resistance to artemisinin derivatives or piperaquine were identified.

Mathematical Model of Malaria Transmission with Anti-Malarial Herbal Therapy as Control

Conventional anti–malarial drugs (chloroquine, Artesunate, Quinine, Amodiaquine etc) are used by most malaria-endemic countries as first-line treatment for uncomplicated malaria. However, resistance by plasmodium parasite against these conventional anti–malarial drugs has necessitated the need for herbal medicine as alternative. So in this study, we formulate a mathematical model of malaria transmission in two interacting population of human (host) and mosquito (vector) incorporating anti-malarial herbal therapy as first line treatment for uncomplicated malaria infection. The region where the model is epidemiological feasible and mathematically well–posed is established and the basic reproduction number R_0 is derived using next generation matrix approach. The numerical experiment carried out to access the impact of the control measure on malaria transmission revealed a reduction in the number of complicated infectious human population. Hence this research work suggests a massive campaign on use of anti-malarial herbal therapy as first- line treatment for malaria infection cases.

Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment.

The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor ap2-g, is known to be influenced by host factors but a comprehensive model remains uncertain. Here, we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission. We examine markers of host immunity and metabolism, and markers of parasite growth and transmission investment. We find that inflammatory responses associated with reduced plasma lysophosphatidylcholine levels are associated with markers of increased investment in parasite sexual reproduction (i.e. transmission investment) and reduced growth (i.e. asexual replication). This association becomes stronger with falling transmission and suggests that parasites can rapidly respond to the within-host environment, which in turn is subject to changing transmission.

The Phenomenon of the ‘Starry Sky’ on Blood: Lesson Learned From Severe Malaria Falciparum

Severe malaria occurs when previously uncomplicated malaria infections are then turn to be full blown and tangled by serious, single or multi-organ failures or abnormalities in the patient's blood or metabolism. Clinical deterioration can happen abruptly and unnoticed, due to the masking of other prominent clinical condition like hyperthermia. Making the correct diagnosis as soon as possible is pivotal before administering antimalarial therapy. Diagnosis is made by examining the thick and thin blood films in an attempt to find malaria parasites in the blood sample.The “Starry Sky” appearance is a microscopic feature of severe malaria infection and its exclusively found only in thick blood film. The aim of this minireview is to discuss about the clinical background of “Starry Sky” appearance found in thick blood smear of severe malaria and its brief review combined with our experience in the Deptartment of Parasitology, Faculty of Medicine Universitas Kristen Indonesia, Jakarta-Indonesia, in handled blood test from a vulnerable patient with severe malaria and how we pass on the lessons from that story to our students as part of health communication in community based Parasitology. By inserting this story to our lesson materials, we hope can build awareness among our students as future health practitioners and also to the public they serve as well as all stake holders; this snow ball action are currently and continously required to be done.

Malaria and its importance in travel medicine

Malaria remains one of the most important infectious diseases worldwide. The annual number of cases is currently estimated at around 240 million globally, of which more than 500,000 cases are fatal. The majority of malaria cases in Europe are imported from the African continent. Plasmodium falciparum, the causative agent of malaria tropica, causes 75-90 % of all infections imported to Germany. Artemisinin-based combination therapies are the standard treatment for uncomplicated malaria worldwide. In addition to uncomplicated malaria infections, Plasmodium falciparum can cause severe malaria, characterized by vital organ dysfunction and hyperparasitaemia. The treatment of choice for severe malaria is parenteral artesunate. For all patients presenting with febrile illness after a stay in a malaria-endemic area malaria must be ruled out immediately. Microscopy of the thick drop remains the gold standard for diagnosis in clinical routine.

The antimalarial activity of 1,2,4-trioxolane/trioxane hybrids and dimers: A review.

Malaria, a mosquito-borne parasitic infection caused by protozoan parasites belonging to the genus Plasmodium, is a dangerous disease that contributes to millions of hospital visits and hundreds and thousands of deaths across the world, especially in Sub-Saharan Africa. Antimalarial agents are vital for treating malaria and controlling transmission, and 1,2,4-trioxolane/trioxane-containing agents, especially artemisinin and its derivatives, own antimalarial efficacy and low toxicity with unique mechanisms of action. Moreover, artemisinin-based combination therapies were recommended by the World Health Organization as the first-line treatment for uncomplicated malaria infection and have remained as the mainstay of the treatment of malaria, demonstrating that 1,2,4-trioxolane/trioxane derivatives are useful prototypes for the control and eradication of malaria. However, malaria parasites have already developed resistance to almost all of the currently available antimalarial agents, creating an urgent need for the search of novel pharmaceutical interventions for malaria. The purpose of this review article is to provide an emphasis on the current scenario (January 2012 to January 2022) of 1,2,4-trioxolane/trioxane hybrids and dimers with potential antimalarial activity and the structure-activity relationships are also discussed to facilitate further rational design of more effective candidates.

COMPARATIVE STUDY OF IN VITRO ANTIOXIDANT ACTIVITIES OF PETROLEUM ETHER, ACETONE AND ETHANOL EXTRACTS OF THE AERIAL OF ACANTHOSPERMUM HISPIDUM

Acanthospermum hispidum is used ethnomedicinally for the treatment of acute tuberculosis, typhoid, jaundice, diarrhoea, cough, dysentery and pneumonia, uncomplicated malaria and other parasitic infections. A. hispidum has been used widely in traditional medicine for years by Nigerians but with fewer records of the antioxidant activities of its aerial part. The aim of the study was to evaluate the antioxidant activity of three solvent extracts of the aerial part of the plant. In this study the aerial part of A. hispidum was extracted with three different solvents (petroleum ether, acetone and ethanol) and were evaluated for their in vitro antioxidant activities. Four methods were used for the evaluation: the Thiobarbituric Acid (TBA), Ferric Thiocyanate (FTC) and reducing power methods and also the direct measurement of DPPH radical scavenging activity. Among the three extracts, the acetone extract had the utmost antioxidant activity as revealed by reducing power assay, greater free radical scavenging activity as shown by the DPPH, and also higher antioxidant activity as indicated by the TBA method.The current study clearly reveals the prospective antioxidant activity and free radical scavenging properties of A. hispidum extracts. This may be as a result of the numerous functional compounds present in the aerial part as shown which may be an important source of natural antioxidant, and might be supportive in checking the progress of several oxidative stresses.&#x0D; Acanthospermum hispidum is used ethnomedicinally for the treatment of acute tuberculosis, typhoid, jaundice, diarrhoea, cough, dysentery and pneumonia, uncomplicated malaria and other parasitic infections. A. hispidum has been used widely in traditional medicine for years by Nigerians but with fewer records of the antioxidant activities of its aerial part. The aim of the study was to evaluate the antioxidant activity of three solvent extracts of the aerial part of the plant. In this study the aerial part of A. hispidum was extracted with three different solvents (petroleum ether, acetone and ethanol) and were evaluated for their in vitro antioxidant activities. Four methods were used for the evaluation: the Thiobarbituric Acid (TBA), Ferric Thiocyanate (FTC) and reducing power methods and also the direct measurement of DPPH radical scavenging activity. Among the three extracts, the acetone extract had the utmost antioxidant activity as revealed by reducing power assay, greater free radical scavenging activity as shown by the DPPH, and also higher antioxidant activity as indicated by the TBA method.The current study clearly reveals the prospective antioxidant activity and free radical scavenging properties of A. hispidum extracts. This may be as a result of the numerous functional compounds present in the aerial part as shown which may be an important source of natural antioxidant, and might be supportive in checking the progress of several oxidative stresses.

Abstract 124: The Immunometabolic Role Of Platelets In Uncomplicated Malaria Infection

The malaria causing Plasmodium parasite is a major public health threat. Plasmodium vivax (P vivax) is the cause of uncomplicated malaria (UCM). Platelets are the cellular mediators of thrombosis and are also the most numerous immune cells in the blood, and a first responder to infections. Thrombocytopenia is a frequent complication of malaria, and a decrease in platelet count is a negative predictor of disease outcome. Malaria infection elicits a strong interferon gamma (IFNγ) response. IFNγ is a potent inducer of indoleamine 2,3-dioxygenase (IDO1) the rate-limiting enzyme that catalyzes the first step in Tryptophan (Trp) metabolism in the kynurenine (Kyn) pathway, shunting Trp away from serotonin production. Trp metabolism may be altered in malaria infection as a means to regulate immunometabolic responses, but the mechanisms remain unknown. Our platelet RNA-sequencing data from P vivax infected humans and from P yoelii infected mice showed increased expression of genes related to Trp metabolism, including IDO1 . The role for platelets in metabolic pathway regulation is poorly explored in general, but particularly in infectious diseases. We introduce a novel idea that platelets participate in immunometabolism to infection. Using complementary experimental approaches such as liquid chromatography-mass spectrometry, ELISA, PCR, western blot, and flow cytometry, we test the hypothesis that platelets are a source of IDO1 in UCM malaria, and thrombocytopenia results in IDO1 depletion and immune dysregulation. We have discovered a role for platelets in Trp metabolic pathway regulation and that platelet regulated immune responses to malaria infection are in part dependent on the Trp metabolic pathways. During P yoelii infection there is a depletion of Trp, and increased Kyn metabolites, as well as decreased plasma serotonin. Platelet transfusions to infected mice can increase Kyn. Understanding the interplay between platelets and immunometabolic pathways may provide a better understanding of the impact of thrombocytopenia in diseases beyond malaria, and provide a means to improve malaria infection responses as well as improved platelet-directed therapeutics in many hematological, metabolic, and immune diseases .

Cardiopulmonary alterations by ultrasound in a patient with uncomplicated mixed malaria infection: a case report from the Amazon Basin

BackgroundInformation on cardiopulmonary complications in clinical malaria is sparse and diagnosis may be difficult in resource-limited areas due to lack of proper diagnostic tools and access to medical care. A case of pericardial effusion and pulmonary alterations assessed by ultrasound in a patient with uncomplicated mixed malaria infection is described.Case presentationA previously healthy 23-year-old male from the Amazon Basin was diagnosed with mixed infection of Plasmodium vivax and Plasmodium falciparum by peripheral blood smear. The patient presented with mild malaria symptoms without signs of severe malaria, but reported moderate chest pain and shortness of breath. Laboratory analyses revealed thrombocytopenia and anemia. The electrocardiogram had PR depressions and bedside ultrasound of the cardiopulmonary system showed pericardial effusion (18 mm) accompanied by multiple B-lines in the lungs, identified as vertical artifacts extending from the pleural line. Cardiac biomarkers were normal. The patient was treated according to national guidelines for malaria and suspected pericarditis, respectively. At follow-up on day 5, the pericardial effusion (9mm) and B-lines had markedly decreased. By day 21 the patient was asymptomatic, had completed the treatment, and the electrocardiogram and ultrasound findings had normalized.ConclusionsThis case report highlight the usefulness of bedside ultrasound to identify cardiopulmonary involvement in patients with uncomplicated malaria and relevant symptoms.

Study towards improving artemisinin-based combination therapies.

Covering: Up to 2020 Artemisinin has made a significant contribution towards global malaria control since its initial discovery. Countless lives have been saved by this unique and miraculous molecule. In 2006, artemisinin-based combination therapies (ACTs) were recommended by the World Health Organization (WHO) as the first-line treatment for uncomplicated malaria infection and have since remained as the mainstays of the antimalarial treatment. Even so, substantial efforts to pursue better curative effects for the treatment of malaria have never ceased, particularly with regards to the circumstances surrounding the appearance of delayed clearance of malaria parasites by 3 day ACT treatments in South-East Asian countries. Strategies to further optimize artemisinin-based therapies, including synthesizing better artemisinin derivatives, developing advanced drug delivery systems, and diversifying artemisinin partner drugs, have been proposed over the past few years. Here, we provide an updated account of the continuous efforts in improving ACTs for better efficacy in curing malarial infection.

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

BackgroundMalaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection.MethodsA systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013.ResultsOf the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001).ConclusionsThe risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

Genetic Diversity and Multiplicity of Infection in Plasmodium Falciparum Isolates Causing Uncomplicated Malaria Infections in North-East India

Understanding the genetic diversity of Plasmodium falciparum still remains a major obstacle in developing effective malaria control strategies in different geographical regions of North East India. The study was aimed to determine the genetic diversity of P. falciparum merozoite surface protein 1 (mspl) and 2 (msp2) and multiplicity of infection (MOl) from uncomplicated malaria patients from the states of Assam, Manipur and Meghalaya in North East India. A total of sixty six P. falciparum isolates from uncomplicated malaria patients attending various public health centers of northeastern states were collected from September 2015 to December 2018 prior to treatment. Parasite DNA was extracted and mspl and msp2 gene frequencies and diversity were analyzed using allele-specific nested PCR assay followed by sequencmg. Analysis of mspl alleles revealed that Kl allelic family was predominant with 33.34% followed by MAD20 at 18.18%% and R033 at 9.09% respectively. In msp2, the 3D7 family was most highly represented with 50% prevalence against 31.81% for FC27. Multiclonal infections were observed with 26 (39.40%) and 12 (18.18%) patients harboring more than one parasite genotype followed by MOl at 1.12 and 0.95 for mspl and msp2 genes respectively. The present study showed the highest genetic diversity in P. falciparum infected patients in Assam state with multiple clones followed by Meghalaya and Manipur indicating gene flow between the parasite populations within the states due to frequent human migration.

Clinical Probe of Cyp2C8*2 Mutants in a Malaria Hyperendemic Zone: Evidence from North-Central, Nigeria.

A tremendous level of success has been achieved since the introduction of chloroquine and the combination of amodiaquine and artemisinin for the treatment of both complicated and uncomplicated malaria infections in sub-Saharan Africa. However, the recent discovery of drug resistant strains of Plasmodium falciparum (P.f.) and the ability of the parasite to ingest CYP2C8 into its digestive vacuole is of great public health concern. This study probes the occurrence of CYP2C8*2 allelic mutant amongst malaria patients in North-Central Nigeria. Three hundred and eighty five (385) unrelated study participants were screened for current malaria episodes using routine microscopy and/or rapid diagnostic test strips (RDTs). Chelex extraction method was used for single nucleotide polymorphisms (SNPs) and identification of CYP2C8*2 (805A > T) variant respectively. Wild-type (A) and the defective allele (T) were differentiated with the use of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The results obtained were further validated with Sanger sequencing of a few samples and thereafter, the genotype data were statistically processed. All alleles obtained were in Hardy Weinberg equilibrium. Out of the 385 participants (45.5% Male and 54.5% Female) genotyped for SNPs, 75 (19.5%) had the autosomal recessive mutant trait. Occurrence of mutant traits was gender and ethnic independent (p > 0.05). Yoruba ethnic group recorded a reduction in proportion of genotypic defective CYP2C8*2 allele (T) (1 in every 8 persons) with a carrier percentage of 13.3% compared with Hausa (26.62%); Igbo (25.37%) and other minority ethnic groups (17.6%). A remarkable inter-ethnic differences in autosomal recessive CYP2C8*2 allele was observed. By implication, there is a gradual incursion of genetic drift for poor CQ and AQ-Artemisinin metabolizers among the inhabitants.

Fever in the returning traveller : dual infection with SARS-CoV-2 and Plasmodium falciparum malaria

Background: More than 90% of the global 400 000 annual malaria deaths occur in Africa. The current SARS-CoV-2 pandemic has resulted in more than 830 000 deaths in its first 10 months. Case presentation: This case describes a patient who had travelled from Mozambique to Cape Town, presented with a mild febrile illness, and was diagnosed with both COVID-19 and uncomplicated Plasmodium falciparum malaria infection. She responded well to malaria treatment and had an uneventful COVID-19 admission. Her blood smear showed a low malaria parasitaemia and a relatively high gametocyte load. Conclusion: We postulate that her clinical course and abnormal smear could well be due to reciprocal disease-modifying effects of the infections. The presenting symptoms of COVID-19 may mimic endemic infectious diseases including malaria, tuberculosis, pneumocystis pneumonia and influenza thus there is a need for clinical vigilance to identify and treat such co-infections.

Genetic diversity of Plasmodium falciparum isolates from patients with uncomplicated and severe malaria based on msp-1 and msp-2 genes in Gublak, North West Ethiopia

BackgroundMalaria infection can present with a wide variety of symptoms, ranging from mild to severe. Plasmodium falciparum isolates in uncomplicated and severe malaria infections may have different parasite genetic profiles. This study was conducted to assess differences in genetic diversity and allelic frequencies in P. falciparum isolates according to malaria severity and age of patients in the Gublack area, northwest Ethiopia.MethodsCross-sectional health facility-based study conducted in Gublak, Ethiopia between July, 2017 and October, 2017. Symptomatic P. falciparum malaria patients with microscopically-confirmed infection were enrolled. Parasite DNA was extracted from filter paper blood spots and the polymorphic regions of the msp-1 and msp-2 genes were genotyped using allele-specific nested-PCR with fragment analysis by gel electrophoresis.ResultsA total of 118 patients were enrolled including 95 (80.5%) with uncomplicated infection and 23 (19.5%) with severe disease. In msp-1, the K1 allelic family was similarly prevalent in uncomplicated 42 (44.2%) and severe disease 12 (52.2%). In msp-2, FC27 was detected in 55 (57.9%) of uncomplicated infections and IC/3D7 in 14 (60.9%) of severe infections. 76 (64.4%) of the 118 isolates contained multiple genotypes; 56 (58.9%) in uncomplicated infections and 19 (82.6%) in severe infections. The overall of multiplicity of infection was 2.2 (95% CI 1.98–2.42) with 1.4 (95% CI 1.23–1.55) and 1.7 (95% CI 1.49–1.86) for msp-1 and msp-2, respectively. Multiplicity of infection was significantly higher in severe than uncomplicated infections (3.0 (95% CI 2.61–3.47) versus 2.0 (95% CI 1.83–2.23), respectively, p = 0.001). There was no difference in multiplicity of infection across age groups (p = 0.104).ConclusionPatients with severe malaria were more likely to have multiclonal infections. Further studies are needed to describe the association between P. falciparum genotypes and malaria severity in different malaria transmission areas.

Diagnostic performance of CareStart\u2122 malaria HRP2/pLDH test in comparison with standard microscopy for detection of uncomplicated malaria infection among symptomatic patients, Eastern Coast of Tanzania

BackgroundCareStart™ malaria HRP2/pLDH (Pf/pan) combo test is one of the several rapid diagnostic tests (RDT) approved for diagnosis of malaria at the point of care in Tanzania. However, there are limited studies on the diagnostic performance of RDT after wide scale use in primary health care facilities in Tanzania. Therefore, this study was carried out to determine the diagnostic performance of RDT when compared with blood smear (BS) microscopy as a reference standard.MethodsA cross-sectional study was conducted between March and August 2019 at Kibiti Health Centre, Pwani region, Tanzania. Blood samples for malaria tests were collected from patients with malaria symptoms. Diagnostic performance parameters of RDT, i.e. sensitivity, specificity, positive and negative likelihood ratios (LR+/−), diagnostic accuracy and predictive values were determined using contingency table. An agreement between RDT and microscopy was statistically determined by Cohen’s kappa test.ResultsOf 980 patients screened, 567 (57.9%) were found to be malaria positive by RDT, whereas 510 patients (52%) were positive by microscopy. Of the 510 microscopy-positive patients, 487 (95.5%) were infected with Plasmodium falciparum. The geometric mean parasite density was 2921parasites/µl, whereas majority (68.6%) of patients had parasite density greater than 10,000/µl. The sensitivity, specificity, positive and negative predictive values of CareStart™ were 99.8%, 87.6%, 89.8%, and 99.8%, respectively. The LR+ and LR− were 8.0 and 0.002, respectively. The diagnostic accuracy was 0.5. There was a strong agreement between the results obtained using CareStart™ and BS microscopy (kappa = 0.863, P < 0.0001).ConclusionCareStart™ malaria HRP2/pLDH (Pf/pan) had high sensitivity and strong agreement with microscopy results. However, moderate specificity of RDT resulted in a substantial number of patients with false positive malaria test. Wherever available, microscopy should be used to confirm RDT test results.